Oral Squamous Cell Carcinoma (OSCC), Oropharyngeal Squamous Cell Carcinoma (SCC), Stereotactic Body Radiation Therapy (SBRT)
Conditions
Keywords
Oral Squamous Cell Carcinoma (OSCC), Oropharyngeal Squamous Cell Carcinoma (SCC), Stereotactic Body Radiation Therapy (SBRT), Toripalimab, Phase II Clinical Trial
Brief summary
In this study, participants will be randomly assigned to either the experimental group or the control group. The experimental group will first receive SBRT (6Gy\*3 fractions) to treat the primary tumor and metastatic lymph nodes. This will be followed by a combination of Toripalimab, Docetaxel, and Cisplatin for three cycles, every three weeks. The control group will receive the same combination of Toripalimab, Docetaxel, and Cisplatin for three cycles, every three weeks, but without SBRT. After the final round of chemotherapy, all participants will have imaging scans and, three weeks later, undergo surgery. After surgery, they may also receive additional radiotherapy with or without chemotherapy. Patients can also choose whether to continue treatment with Toripalimab after surgery.
Detailed description
Participants will be randomly assigned to the experimental group and the control group. The experimental group will first receive SBRT (Stereotactic Body Radiotherapy) for the primary tumor and positive lymph nodes (prescribed dose: 6 Gy × 3 fractions, once every other day). One to two weeks after SBRT, they will receive 240 mg of Toripalimab + 75 mg/m² of Docetaxel + 75 mg/m² of Cisplatin, administered every 3 weeks for 3 cycles. The control group will receive 240 mg of Toripalimab + 75 mg/m² of Docetaxel + 75 mg/m² of Cisplatin, administered every 3 weeks for 3 cycles. Both groups will undergo imaging assessment 2 weeks after the final chemotherapy cycle. Three weeks after the last chemotherapy cycle, participants will receive curative surgery. Postoperative adjuvant radiotherapy ± chemotherapy will be administered according to preoperative staging and postoperative pathological characteristics. Patients may also choose to continue maintenance treatment with Toripalimab after surgery.
Interventions
RADIATIONSBRT
The experimental group will first receive SBRT (Stereotactic Body Radiotherapy) for the primary tumor and positive lymph nodes (prescribed dose: 6 Gy × 3 fractions, once every other day).
DRUGDocetaxel, Cisplatin, Toripalimab
Toripalimab 240mg (free medicine) + Docetaxel 75mg/m2 + Cisplatin 75mg/m2, q3w for 3 courses
PROCEDURERadical resection surgery
Radical resection surgery
RADIATIONIMRT ± chemotherapy/toripalimab
According to the preoperative staging and postoperative pathological characteristics, all patients will receive postoperative radiotherapy with or without cisplatin-based chemotherapy. Additionally, patients can choose whether to continue maintenance therapy with toripalimab after surgery.
Sponsors
Hospital of Stomatology, Sun Yat-Sen University
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Oral/oropharyngeal squamous cell carcinoma confirmed by histology and/or cytology. 2. Clinical stage: resectable oral/oropharyngeal squamous cell carcinoma stage III-IVa (AJCC 8th edition) 3. Age: 18-65 years old. 4. According to the Eastern Cooperative Oncology Group (ECOG) criteria (performance status score of 0 or 1). 5. Good organ function: A. Hematology: WBC ≥ 4000/μL, neutrophil ≥ 2.000/μL, hemoglobin ≥ 9g/dL, platelet ≥ 100000/μL; B. Liver function: bilirubin ≤ 1.5 times the upper limit of normal (ULN) (patients with known Gilbert's disease and serum bilirubin level ≤ 3 times ULN can be included), AST and ALT ≤ 3 times, and alkaline phosphatase ≤ 3 times ULN; albumin ≥ 3g/dL; C. International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 1.5 times; D. Renal function: serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60mL/min according to the Cockcroft-Gault formula. 6. Expected survival ≥ 3 months. 7. The patient has signed an informed consent form and is willing and able to comply with the study visits, treatment plans, laboratory tests and other study procedures. 8. Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days before enrollment and must agree to take effective contraceptive measures during the study and for at least 60 days after the last dose (including chemotherapy drugs and Teplizumab). 9. If the female partner of the male subject is still of childbearing potential, the male subject must agree to take effective contraceptive measures during the study and for at least 60 days after the last dose.
Exclusion criteria
1. Patients with other malignant tumors. 2. Patients with known or suspected autoimmune diseases, including dementia and epilepsy. 3. Patients with severe mental illness. 4. Patients with necrotic lesions and who are assessed by the researchers to be at risk of major bleeding. 5. Patients with severe heart disease, pulmonary dysfunction, heart function and pulmonary function below grade 3 (including grade 3). 6. Patients whose laboratory test values do not meet the relevant standards within 7 days before enrollment. 7. Patients who have received systemic or local glucocorticoid treatment within 4 weeks before enrollment. 8. Patients with complications that require long-term use of immunosuppressive drugs or systemic or local use of corticosteroids with immunosuppressive effects. 9. Patients with active pulmonary tuberculosis (TB) who are currently receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening. 10. Previous use of anti-toripalimab, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell co-stimulation or checkpoint pathway). 11. Subjects with any active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo or complete remission of asthma in childhood and no need for any intervention as adults can be included; patients with asthma requiring medical intervention with bronchodilators cannot be included). 12. HIV positive. 13. HBsAg positive and HBVDNA copy number positive (quantitative detection ≥1000cps/ml); positive blood screening for chronic hepatitis C (HCV antibody positive). 14. Any anti-infection vaccine (such as influenza vaccine, varicella vaccine, etc.) received within 4 weeks before enrollment. 15. Women of childbearing age with positive pregnancy test and breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) | 2 weeks after the surgery | pathological complete response rate after radical resection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | two weeks after the chemoimmunotherapy | The proportion of patients with a 30% reduction in tumor volume is the sum of the complete response (CR) and partial response (PR) rates. |
| Disease-free survival (DFS): | 2 years | The interval from the start of treatment to the earliest treatment failure due to any reason (including local recurrence, regional recurrence, distant metastasis, or death). |
| Major Pathological Response (MPR) | 2 weeks after the surgery | The proportion of patients whose microscopic tumor cells were reduced to less than 10% as assessed by the American Joint Committee on Cancer/College of American Pathologists (AJCC/CAP) tumor regression grade (TRG) scheme for surgical specimens. |
| Mandibular preservation rate: | immediately after the surgery | the proportion of patients with oral cancer whose mandibular continuity is preserved after primary lesion surgery. |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | one month after the postoperative radiotherapy | the proportion of patients with adverse events of grade 3 or above among all patients. |
| Overall survival (OS) | 2 years | the time interval from the start of treatment to death from any cause. |
Countries
China
Contacts
Primary ContactFang-Yun Xie, Principal Investigator
Outcome results
None listed